Research Article: ABCB Regulates Immune Genes in Breast Cancer
Abstract:
Chemoresistance is a major challenge for breast cancer treatment. The mechanisms of chemoresistance are complex because of crosstalk between receptor tyrosine kinases and downstream pathways, deregulation of cell-cycle and apoptosis regulators, and modulation of tumor-infiltrating immune cells. The ATP-binding cassette (ABC) superfamily is one of the largest families of membrane-bound transport proteins in humans. ABC transporters use the energy from ATP hydrolysis to actively pump out substrates through the cell membrane. ABC transporters also function in cell apoptosis, energy metabolism, and material transport. In cancer cells, ABC transporters participate in detoxification and drug resistance. Multidrug resistance protein (MDR; gene: ABC subfamily B, member , ABCB), multidrug resistance-associated protein (MRP; gene: ABC subfamily C, member , ABCC), and breast cancer resistance protein (BCRP; gene: ABC subfamily G, membrane , ABCG) have been studied in chemoresistant breast cancer. Increased expression of ABCB has been reported in recurrent breast cancer, and patients with ABCB-positive cancer fail to respond to chemotherapy. ABCB is also a metastatic marker for triple-negative breast cancer. ABCB is overexpressed in doxorubicin-resistant MCF breast cancer cells. Theoretically, inhibition of ABC transporters during cancer therapy should improve the sensitivity of cancer cells to cytotoxic agents. Several clinical trials of ABCB-reversing agents combined with chemotherapeutic drugs are currently ongoing in cancer patients, but the results have not been satisfactory. No effective ABCB-reversing drug without significant toxicity has been approved., Treatment with doxorubicin also induces ABCB expression and enhances drug efflux potential through FOXOa signaling in K leukemia cells. Non-synergistic effects of chemotherapy agents and ABC-reversing drugs are possible because the downstream pathway of ABCB is complicated. Further study of ABCB in cancer is needed to aid development of potential therapeutic agents.
Introduction:
Chemoresistance is a major challenge for breast cancer treatment. The mechanisms of chemoresistance are complex because of crosstalk between receptor tyrosine kinases and downstream pathways, deregulation of cell-cycle and apoptosis regulators, and modulation of tumor-infiltrating immune cells. The ATP-binding cassette (ABC) superfamily is one of the largest families of membrane-bound transport proteins in humans. ABC transporters use the energy from ATP hydrolysis to actively pump out substrates through the cell…
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